The recent emergence of antibiotic-resistant, Gram-positive bacteria presents a major challenge to today s pharmaceutical industry. Cubist Pharmaceuticals has addressed this challenge with a target-based approach to drug discovery. Cubist uses novel targets, that are essential to the pathogen s viability, in high throughput screening programs to identify potential drug candidates. Here, we present data on the acquisition and characterization of an essential target from the Gram-positive bacterium Staphylococcus aureus and propose experimentation that will lead to the identification of chemical inhibitors of this target via high throughput screening. A thorough characterization and analysis of these inhibitors to determine in vitro sand in vivo mechanisms of action is also planned. Phase II of this project will involve the optimization of these inhibitors to drug candidate status. PROPOSED COMMERCIAL APPLICATION The commercial applicability of this project lies in the recent emergence of drug-resistant Gram-positive bacteria and the ensuing need for a new chemical class of antibiotics. Cubist Pharmaceuticals has taken a target-based approach to the discovery of novel antibiotics. In this proposal we outline a research project that will allow us to identify inhibitors